Assisted Reproductive Technology Conception Research Articles

Upregulated YTHDC1 mediates trophoblastic dysfunction inducing preterm birth in ART conceptions through enhanced RPL37 translation

Assisted reproductive technology (ART) pregnancies present a higher risk of singleton preterm birth than natural pregnancies, but the underlying molecular mechanism remains largely unknown. RNA m6A modification is a key epigenetic mechanism regulating cellular function, but the role of m6A modification, especially its “reader” YTHDC1, in preterm delivery remains undefined. To delineate the role and epigenetic mechanism of m6A modification in ART preterm delivery, the effects of YTHDC1 on trophoblastic function were evaluated by CCK-8, EdU, Transwell, and flow cytometry analyses post its overexpression or knockdown. Downstream signaling pathways of YTHDC1 were investigated by RNA-seq, and targeted mRNAs were explored by RIP-seq and MeRIP-seq. Upstream transcriptional factors of YTHDC1 were determined by ChIP-seq and luciferase reporter assays. Elevated YTHDC1 was detected in human ART-conceived preterm placentas and in murine preterm placentas post estradiol (E2) exposure. In vitro experiments showed that YTHDC1 promoted trophoblastic cell proliferation and migration, but inhibited cell apoptosis. Mechanistically, E2 was proven to upregulate YTHDC1 expression via retinoid X receptor alpha (RXRA) in trophoblastic cells. Enhanced YTHDC1 expression augmented the translation of RPL37 in an m6A-dependent manner by binding to m6A-modified RPL37 mRNA and concomitantly promoted the overall translational output. Importantly, administration of siRNA targeting YTHDC1 effectively delayed the progression of preterm delivery. In conclusion, the identified E2/RXRA/YTHDC1/RPL37 axis provides new insights into the epigenetic mechanism underlying ART-associated preterm delivery. The findings offer a potential prognostic biomarker and therapeutic target for preterm delivery.

Assisted reproductive technology and the risk of birth defects mediated by multifetal pregnancy: evidence from the China Birth Cohort Study

BackgroundBoth assisted reproductive technology (ART) and multifetal pregnancy have been reported to be associated with an increased risk of birth defects (BDs). However, it is unclear whether multifetal pregnancy is a mediator that increases the risk of BDs in ART-conceived pregnancies. ObjectivesTo investigate the risk of BDs associated with ART, and to quantify the mediating effect of multifetal pregnancy between ART and BDs. Study DesignFrom November 2017 to August 2021, 132,386 pregnant women from 50 study sites in 17 provinces of China were monitored from their first trimester until delivery (or miscarriage/termination). BDs were detected in both live births and stillbirths. Directed acyclic graph was drawn to understand the causal relationship between ART and BDs, and inverse probability of treatment weighting was used to adjust for confounders. Then, log-binomial generalized estimating equation was established in the inverse probability weighted cohort to estimate the adjusted relative risk (RR) of BDs associated with ART compared to natural conception, while addressing the cluster effect of study sites. Mediation analysis was performed to assess the mediating effect of multifetal pregnancy between ART and BDs. Number needed to harm was calculated for multifetal pregnancy versus singleton pregnancy among ART-conceived pregnancies. ResultsA total of 126,035 naturally conceived and 5124 ART-conceived pregnancies were included in the analysis. The incidence of BDs in the ART conception group (4.2%) was significantly higher than that in the natural conception group (2.5%), with an adjusted RR of 1.48 (95% CI, 1.24 to 1.78). Multifetal pregnancies were also more common in the ART conception group (21.4%) than the natural conception group (1.1%). Mediation through multifetal pregnancy accounted for 25% of the risk of BDs associated with ART. Notably, if ART-conceived pregnant women could have singleton pregnancy rather than multifetal pregnancy, one case of BDs could be potentially avoided for every 52 (95% CI, 29 to 233) pregnancies. ConclusionsMultifetal pregnancy mediated the effect of ART on BDs. Therefore, when ART treatment is needed, single embryo transfer should be considered under clinically feasible conditions for the prevention of BDs.

Risks of Placental Abruption and Preterm Delivery in Patients Undergoing Assisted Reproduction

Patients using assisted reproductive technology (ART) may need additional counseling about the increased risks of placental abruption and preterm delivery. Further investigation into the potential additive risk of ART and placental abruption is needed. To ascertain the risk of placental abruption in patients who conceived with ART and to evaluate if placental abruption and ART conception are associated with an increased risk of preterm delivery (<37 weeks' gestation) over and above the risks conferred by each factor alone. This cross-sectional study used data from the National Inpatient Sample, which includes data from all-payer hospital inpatient discharges from 48 states across the US. Participants included women aged 15 to 54 years who delivered from 2000 through 2019. Data were analyzed from January 17 to April 18, 2024. Pregnancies conceived with ART. Risks of placental abruption and preterm delivery in ART conception compared with spontaneous conceptions. Associations were expressed as odds ratios (ORs) and 95% CIs derived from weighted logistic regression models before and after adjusting for confounders. The relative excess risk due to interaction (RERI) of the risk of preterm delivery based on ART conception and placental abruption was also assessed. Of 78 901 058 deliveries, the mean (SD) maternal age was 27.9 (6.0) years, and 9 212 117 patients (11.7%) were Black individuals, 14 878 539 (18.9%) were Hispanic individuals, 34 899 594 (44.2%) were White individuals, and 19 910 807 (25.2%) were individuals of other races and ethnicities. Of the total hospital deliveries, 98.2% were singleton pregnancies, 68.8% were vaginal deliveries, and 52.1% were covered by private insurance. The risks of placental abruption among spontaneous and ART conceptions were 11 and 17 per 1000 hospital discharges, respectively. After adjusting for confounders, the adjusted OR (AOR) of placental abruption was 1.42 (95% CI, 1.34-1.51) in ART pregnancies compared with spontaneous conceptions, with increased odds in White women (AOR, 1.42; 95% CI, 1.31-1.53) compared with Black women (AOR, 1.16; 95% CI, 0.93-1.44). The odds of preterm delivery were significantly higher in pregnancies conceived by ART compared with spontaneous conceptions (AOR, 1.46; 95% CI, 1.42-1.51). The risk of preterm delivery increased when patients had both ART conception and placental abruption (RERI, 2.0; 95% CI, 0.5-3.5). In this cross-sectional study, patients who conceived using ART and developed placental abruption had a greater risk of preterm delivery compared with spontaneous conception without placental abruption. These findings have implications for counseling patients who seek infertility treatment and obstetrical management of ART pregnancies.

The role of multiple birth and birth complications in the association between assisted reproductive technology conception and autism diagnosis.

In recent decades, the use of assisted reproductive technology (ART) has increased rapidly. To assess the relationship between ART and autism diagnosis, we linked California birth records from 2000 through 2016 with contemporaneous records from the National ART Surveillance System (NASS) and autism caseload records from California's Department of Developmental Services from 2000 through November 2019. All 95 149 birth records that were successfully linked to a NASS record, indicating an ART birth, were matched 1:1 using propensity scores to non-ART births. We calculated the hazard risk ratio for autism diagnosis and the proportions of the relationship between ART conception and autism diagnosis mediated by multiple birth pregnancy and related birth complications. The hazard risk ratio for autism diagnosis following ART compared with non-ART conception is 1.26 (95% CI, 1.17-1.35). Multiple birth, preterm birth, and cesarean delivery jointly mediate 77.9% of the relationship between ART conception and autism diagnosis. Thus, increased use of single embryo transfer in the United States to reduce multiple births and related birth complications may be a strategy to address the risk of autism diagnosis among ART-conceived children.

Combined effects of pre-pregnancy BMI and gestational weight gain on preterm birth: comparison between spontaneous and ART conception.

Inappropriate pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) are both linked to preterm birth (PTB); however, which one plays a dominant role in PTB risk is not yet sure. We aimed to evaluate the combined effect of pre-pregnancy BMI and GWG on the risk of PTB in singleton pregnancies conceived both spontaneously and through assisted reproductive technology (ART). The data included all mothers (n = 17,540,977) who had a live singleton birth from the US National Vital Statistics System (NVSS) 2015-2019. Logistic regression models, quantile-g-computation, and generalized additive model were used to analyze the combined association of pre-pregnancy BMI and GWG with PTB. The singleton PTB rate was significantly higher in ART pregnancies (11.5%) than in non-ART pregnancies (7.9%). When compared to those women with pre-pregnancy normal weight and GWG within Institute of Medicine (IOM) guidelines, the highest PTB risk was observed in non-ART women with pre-pregnancy underweight and GWG below IOM guidelines (aOR 2.56; 95% CI 2.53-2.60) and in ART women with pre-pregnancy obese and GWG below IOM guidelines (aOR 2.56; 95%CI 2.36-2.78). GWG dominated the combined effect with its joint effect coefficient of - 0.281 (P < 0.05) in non-ART women and - 0.108 (P < 0.05) in ART women. Inappropriate GWG played a dominant role in increasing the risk of PTB in both non-ART and ART populations. Counseling regarding pre-pregnancy BMI and especially GWG appears to be even more crucial for pregnancies conceived via ART, given their impact on PTB.

Risk factors for infant formula usage during the initial hospital stay in term and late pre-term neonates after implementation of a breastfeeding support program: A retrospective case–control study from a tertiary care hospital

Background: Infant formula usage in hospitals is inevitable in certain circumstances. We explored the high-risk groups who required formula during hospital stays during the post-intervention phase of a quality improvement initiative for improving exclusive breastfeeding (EBF) rates in hospitals. Methods: A retrospective and case–control study was conducted involving 50 cases of neonates who received infant formula and 200 control who were exclusively breastfed. Data regarding maternal and neonatal details were from breastfeeding assessment forms and case record which was collected prospectively during the program. We compared common risk factors between the two groups. Results: There was a strong association between infant formula usage and cesarean sections, assisted reproductive technology (ART) conceptions, multiple gestations, neonatal intensive care unit admissions, being small for gestational age, and being an infant of a diabetic mother. First-h breastfeeding was associated with a higher likelihood of EBF in the hospital. In the final model, ART conception, multiple gestations, and delayed initiation of breastfeeding were strong predictors of the use of infant formula in the hospital. Conclusion: Initiating breastfeeding within the 1st h promotes EBF. ART conception and multiple gestations remain strong risk factors for formula usage, the social, physiological, and genetic reasons for which will need to be studied in detail.

Maternal Risk of Cardiovascular Disease After Use of Assisted Reproductive Technologies

The use of assisted reproductive technologies (ARTs) is steadily increasing worldwide. The outcomes associated with treatment for an individual's long-term health, including risk of cardiovascular disease (CVD), remain largely unknown, due to the small number of studies and their limited follow-up time. To study whether the risk of CVD is increased among individuals who have given birth after ART compared with those who have given birth without ART. A registry-based cohort study was conducted using nationwide data from Denmark (1994-2014), Finland (1990-2014), Norway (1984-2015), and Sweden (1985-2015). Data analysis was conducted from January to August 2022. A total of 2 496 441 individuals with a registered delivery in the national birth registries during the study period were included, and 97 474 (4%) of these gave birth after ART. Data on ART conception were available from ART quality registries and/or medical birth registries. Information on CVD was available from patient and cause of death registries. The risk of CVD was estimated with Cox proportional hazards regression, adjusting for age, calendar year of start of follow-up, parity, diagnosis of polycystic ovary syndrome, diabetes, chronic hypertension, and country. Median follow-up was 11 (IQR, 5-18) years. The mean (SD) age of women with no use of ART was 29.1 (4.9) years, and the age of those who used ART was 33.8 (4.7) years. The rate of any CVD was 153 per 100 000 person-years. Individuals who gave birth after using ART had no increased risk of CVD (adjusted hazard ratio [AHR], 0.97; 95% CI, 0.91-1.02), with evidence of heterogeneity between the countries (I2 = 76%; P = .01 for heterogeneity). No significant differences in the risk of ischemic heart disease, cerebrovascular disease, stroke, cardiomyopathy, heart failure, pulmonary embolism, or deep vein thrombosis were noted with use of ART. However, there was a tendency for a modest reduction in the risk of myocardial infarction (AHR, 0.80; 95% CI, 0.65-0.99), with no notable heterogeneity between countries. The findings of this study suggest that women who gave birth after ART were not at increased risk of CVD over a median follow-up of 11 years compared with those who conceived without ART. Longer-term studies are needed to further examine whether ART is associated with higher risk of CVD.

Effects of uterine polyps on embryo implantation in IVF cycles

Embryo implantation requires healthy uterine endometrium for natural or assisted reproductive technology conception. However, in presence of any endometrial anatomical abnormality or disease, implantation is affected. Uterine or endometrial polyps are over growths of endometrial cells that extend into the uterine cavity. They are usually noncancerous. There can be one or many polyps. They range in size from a few millimeters to several centimeters or larger. They may cause vaginal bleeding in between periods, heavy periods, frequent or unpredictable periods and infertility. The objective of this study was to find out effects of endometrial polyps on embryo implantation in assisted reproductive technology cycles of Saudi women being treated at an infertility clinic. This was a case-control study. The participants were in ratio of 5:1 i.e., for every 5 patients there was one control. The polyp diagnosis was carried out with ultrasound and endometrial biopsy. We observed high incidence of implantation failure in patients with uterine polyps as compared to that in the control patients. The results of this study indicated that the presence of endometrial polyps is a risk factor for infertility and failure of conception after in vitro fertilization.

Effects of Particulate Matter on the Risk of Gestational Hypertensive Disorders and Their Progression.

Associations between particulate matter (PM) and gestational hypertensive disorders (GHDs) are well documented, but there is no evidence on the associations between PM and GHD progression, especially among those with assisted reproductive technology (ART) conceptions. To explore the effects of PM on the risk of GHDs and their progression among pregnant women with natural or ART conception, we enrolled 185,140 pregnant women during 2014-2020 in Shanghai and estimated the associations during different periods using multivariate logistic regression. During the 3 months of preconception, 10 μg/m3 increases in PM concentrations were associated with increased risks of gestational hypertension (GH) (PM2.5: aOR = 1.076, 95% CI: 1.034-1.120; PM10: aOR = 1.042, 95% CI: 1.006-1.079) and preeclampsia (PM2.5: aOR = 1.064, 95% CI: 1.008-1.122; PM10: aOR = 1.048, 95% CI: 1.006-1.092 ) among women with natural conception. Furthermore, for women with ART conceptions who suffered current GHD, 10 μg/m3 increases in PM concentrations in the third trimester elevated the risk of progression (PM2.5: aOR = 1.156, 95% CI: 1.022-1.306 ; PM10: aOR = 1.134, 95% CI: 1.013-1.270). In summary, women with natural conception should avoid preconceptional PM exposure to protect themselves from GH and preeclampsia. For women with ART conceptions suffering from GHD, it is necessary to avoid PM exposure in late pregnancy to prevent the disease from progressing.

The Effect of an eHealth Coaching Program (Smarter Pregnancy) on Attitudes and Practices Toward Periconception Lifestyle Behaviors in Women Attempting Pregnancy: Prospective Study.

Lifestyle behaviors during the periconception period contribute to achievement of a successful pregnancy. Assessment of attitudes and practices toward these modifiable behaviors can aid in identifying gaps in unhealthy lifestyle behaviors with impact on intervention effectiveness. This study investigates the effectiveness of coaching by the eHealth program Smarter Pregnancy during the periconception period on improvement of attitudes and practices toward fruit and vegetable intake and smoking in women attempting pregnancy through assisted reproductive technology (ART) or natural conception. Women attempting pregnancy through ART (n=1060) or natural conception (n=631) were selected during the periconception period. The intervention groups, conceived through ART or naturally, received Smarter Pregnancy coaching for 24 weeks, whereas the control group conceived through ART and did not receive coaching. Attitudes and practices at baseline and follow-up periods were obtained from self-administered online questionnaire provided by the program. Attitudes were assessed in women with unhealthy behaviors as their intention to increase their fruit and vegetable intake and to quit smoking using a yes/no question. Outcomes on practices, suggesting effectiveness, included daily fruit (pieces) and vegetable (grams) intake, and if women smoked (yes/no). Changes in attitudes and practices were compared at 12 and 24 weeks with baseline between the ART intervention and ART control groups, and within the intervention groups between ART and natural conception. Changes in practices at 12 and 24 weeks were also compared with baseline between women with negative attitude and positive attitude within the intervention groups: ART and natural conception. Analysis was performed using linear and logistic regression models adjusted for maternal confounders and baseline attitudes and practices. The ART intervention group showed higher vegetable intake and lower odds for negative attitudes toward vegetable intake after 12 weeks (βadj=25.72 g, P<.001; adjusted odds ratio [ORadj] 0.24, P<.001) and 24 weeks of coaching (βadj=23.84 g, P<.001; ORadj 0.28, P<.001) compared with ART controls. No statistically significant effect was observed on attitudes and practices toward fruit intake (12 weeks: P=.16 and .08, respectively; 24 weeks: P=.16 and .08, respectively) and smoking behavior (12 weeks: P=.87; 24 weeks: P=.92). No difference was observed for the studied attitudes and practices between the ART intervention and natural conception intervention groups. Women with persistent negative attitude toward fruit and vegetable intake at week 12 showed lower fruit and vegetable intake at week 24 compared with women with positive attitude (βadj=-.49, P<.001; βadj=-30.07, P<.001, respectively). The eHealth Smarter Pregnancy program may improve vegetable intake-related attitudes and practices in women undergoing ART treatment. Women with no intention to increase fruit and vegetable intake had less improvement in their intakes. Despite small changes, this study demonstrates again that Smarter Pregnancy can be used to improve vegetable intake, which can complemented by blended care that combines face-to-face and online care to also improve fruit intake and smoking behavior.

Neurodevelopmental Disorders in Offspring Conceived via In Vitro Fertilization vs Intracytoplasmic Sperm Injection

Intracytoplasmic sperm injection (ICSI), the most common type of assisted reproductive technology (ART), might damage the sperm or embryo. The implications of male infertility and ICSI for the neurodevelopmental health of offspring remain unknown. To analyze the risks of neurodevelopmental disorders in offspring of couples with male or female infertility with or without ICSI use. This cohort study was conducted in Taiwan and used information collected from the national population registry data set, national birth data set, and national ART data set for all live singleton births from January 1, 2008, to December 31, 2016. The follow-up period started from the date of birth until the diagnosis of a disorder or December 31, 2018, whichever occurred first. Data were analyzed from July 1, 2021, to August 1, 2022. Male or female infertility with or without ICSI. The outcome was the incidence of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and developmental delay in offspring with ART conception. Taiwan's national population registry data set was used to identify ASD, ADHD, and developmental delay diagnosed in outpatient clinic and hospitalization records. The study included 1 575 971 singleton births (mean [SD] age, 5.87 [2.60] years; 819 389 boys [52.0%]), of whom 1 568 257 (99.5%) had natural conception, 2111 (0.1%) had ART conception with male infertility, and 5603 (0.4%) had ART conception with female infertility. The risks of ASD (adjusted hazard ratio, 2.49; 95% CI, 1.61-3.84; P < .001) and developmental delay (adjusted hazard ratio, 1.92; 95% CI, 1.54-2.39; P < .001) in offspring with ART conception and ICSI use were significantly higher than those in offspring with natural conception. The same results were found in offspring of couples with either male or female infertility and ICSI intervention. Results of this study suggest that male infertility was not associated with an increased risk of neurodevelopmental disorders in offspring. In both male and female infertility groups, ICSI had unfavorable implications for the neurodevelopmental health of offspring in terms of increased risks of ASD and developmental delay.

Association of phthalate exposure with low birth weight in couples conceiving naturally or via assisted reproductive technology in a prospective birth cohort

BackgroundFew studies have investigated the adverse effects of preconception phthalate (PAE) exposure on birth weight in couples receiving assisted reproductive technology (ART) compared to naturally conceived newborns. ObjectivesWe examined the association between parental preconception/prenatal urinary phthalate exposure and low birth weight (LBW) risk in couples who conceived using ART or naturally. MethodsFrom the Jiangsu Birth Cohort Study (China), we recruited 544 couples who conceived after infertility treatment and 940 couples who conceived naturally and gave birth to a singleton infant between November 2014 and December 2019. Seventeen metabolites of phthalate and three metabolites of phthalate alternatives were analyzed in parental spot urine samples. Clinical data were collected from medical records. We used generalized linear models, elastic net regression, Bayesian kernel machine regression, and quantile-based g-computation to examine the individual and joint effects of parental phthalate exposure on birth weight and LBW risk ratios (RR). ResultsThe relationship between parental phthalate exposure and birth weight was consistent between ART and natural conception. Maternal exposure to mono-ethyl phthalate and mono-carboxyisooctyl phthalate was associated with an increased risk of LBW in ART-conceived infants (RR = 1.27; 95 % confidence interval (CI): 1.03, 1.56; and RR = 1.31; 95 % CI: 1.03, 1.67, respectively). In contrast, in the spontaneously conceived infants, higher paternal prenatal concentrations of mono-benzyl phthalate and mono-carboxyisononyl phthalate were associated with a 40 % and 53 % increase in LBW risk, respectively. Exposure to PAE mixtures was associated with LBW in ART-conceived infants, with the effects primarily driven by di-ethyl phthalate, benzylbutyl phthalate, and di-isononyl phthalate metabolites. Sex-specific LBW was observed, with females appearing to be more susceptible than males. ConclusionsMaternal preconception and paternal prenatal exposure to phthalates were associated with increased risk of LBW in infants. Compared with natural conception, ART-conceived fetuses were more sensitive to PAE mixtures, which requires further attention.

Assisted Reproductive Technology and Risk of Childhood Cancers

The number of children born through the use of assisted reproductive technology (ART) has been increasing. These children may have higher risks for epigenetic alteration and adverse perinatal outcomes, which may be associated with childhood cancers. To determine the associations between different modes of conception and childhood cancers and potential mediation by preterm birth and low birth weight. This nationwide, population-based cohort study included registry data from 2 308 016 eligible parents-child triads in Taiwan from January 1, 2004, to December 31, 2017. A total of 1880 children with incident childhood cancer were identified. Data were analyzed between September 1, 2020, and June 30, 2022. Mode of conception, defined as (1) natural conception, (2) subfertility and non-ART (ie, infertility diagnosis but no ART-facilitated conception), or (3) ART (ie, infertility diagnosis and ART-facilitated conception). Diagnosis of childhood cancer according to the International Classification of Childhood Cancers, Third Edition. The mean (SD) paternal and maternal ages were 33.28 (5.07) and 30.83 (4.56) years, respectively. Of the 2 308 016 children, 52.06% were boys, 8.16% were born preterm, and 7.38% had low birth weight. During 14.9 million person-years of follow-up (median, 6 years [IQR, 3-10 years]), ART conception was associated with an increased risk of any type of childhood cancers compared with natural conception (hazard ratio, 1.58; 95% CI, 1.17-2.12) and subfertility with non-ART conception (hazard ratio, 1.42; 95% CI, 1.04-1.95). The increased cancer risk of children conceived with ART was mainly owing to leukemia and hepatic tumor. The increased cancer risk associated with ART conception was not mediated by preterm birth or low birth weight. In this cohort study, children conceived via ART had a higher risk of childhood cancers than those conceived naturally and those born to parents with an infertility diagnosis did not use ART. The increased risk could not be explained by preterm birth or low birth weight.

The Association of Assisted Reproductive Technology and Breastfeeding Rates: A Systematic Review and Meta-Analysis.

Background: There is an inconsistent result regarding the mode of fertilization and breastfeeding. Objective: This systematic review and meta-analysis aimed to determine the association between the mode of conception and breastfeeding continuity. Materials and Methods: The English electronic databases were searched for up to May 20, 2022. The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the included studies. Publication bias was assessed using a funnel plot. The heterogeneity of studies was evaluated using I2 statistics. Results of the random-effects meta-analysis were presented using odds ratios (ORs)/relative ratio (RR) and 95% confidence intervals (CIs). Results: A total of 12 articles with 4,929 subjects were included in this systematic review and meta-analysis. The pool estimates of the meta-analysis show that spontaneous conception is associated with breastfeeding continuity up to 6 months (OR/RR = 0.66, 95% CI: 0.46-0.87) and more than 6 months after childbirth (OR/RR = 0.65, 95% CI: 0.32-0.98) compared to the Assisted reproductive technology (ART) conception. The heterogeneity among the studies was high. The level of breastfeeding, plurality, gestational age, and country were confounding factors that affect the heterogeneity of studies. Conclusion: Our findings confirm an inverse association between ART conception and breastfeeding continuity. Due to the importance of breast milk in improving the health of infants who are born in this way, it is recommended to take appropriate interventions in this field. Possible interaction between ART and breastfeeding continuity in different regions is important to point and future studies on this topic were recommended.

Association of Assisted Reproductive Technology With Offspring Growth and Adiposity From Infancy to Early Adulthood

People conceived using assisted reproductive technology (ART) make up an increasing proportion of the world's population. To investigate the association of ART conception with offspring growth and adiposity from infancy to early adulthood in a large multicohort study. This cohort study used a prespecified coordinated analysis across 26 European, Asia-Pacific, and North American population-based cohort studies that included people born between 1984 and 2018, with mean ages at assessment of growth and adiposity outcomes from 0.6 months to 27.4 years. Data were analyzed between November 2019 and February 2022. Conception by ART (mostly in vitro fertilization, intracytoplasmic sperm injection, and embryo transfer) vs natural conception (NC; without any medically assisted reproduction). The main outcomes were length / height, weight, and body mass index (BMI; calculated as weight in kilograms divided by height in meters squared). Each cohort was analyzed separately with adjustment for maternal BMI, age, smoking, education, parity, and ethnicity and offspring sex and age. Results were combined in random effects meta-analysis for 13 age groups. Up to 158 066 offspring (4329 conceived by ART) were included in each age-group meta-analysis, with between 47.6% to 60.6% females in each cohort. Compared with offspring who were NC, offspring conceived via ART were shorter, lighter, and thinner from infancy to early adolescence, with differences largest at the youngest ages and attenuating with older child age. For example, adjusted mean differences in offspring weight were -0.27 (95% CI, -0.39 to -0.16) SD units at age younger than 3 months, -0.16 (95% CI, -0.22 to -0.09) SD units at age 17 to 23 months, -0.07 (95% CI, -0.10 to -0.04) SD units at age 6 to 9 years, and -0.02 (95% CI, -0.15 to 0.12) SD units at age 14 to 17 years. Smaller offspring size was limited to individuals conceived by fresh but not frozen embryo transfer compared with those who were NC (eg, difference in weight at age 4 to 5 years was -0.14 [95% CI, -0.20 to -0.07] SD units for fresh embryo transfer vs NC and 0.00 [95% CI, -0.15 to 0.15] SD units for frozen embryo transfer vs NC). More marked differences were seen for body fat measurements, and there was imprecise evidence that offspring conceived by ART developed greater adiposity by early adulthood (eg, ART vs NC difference in fat mass index at age older than 17 years: 0.23 [95% CI, -0.04 to 0.50] SD units). These findings suggest that people conceiving or conceived by ART can be reassured that differences in early growth and adiposity are small and no longer evident by late adolescence.

Does being conceived by assisted reproductive technology influence adult quality of life?

Numerous studies have investigated the physical health and development of children and adolescents conceived with assisted reproductive technology (ART). Less is known about the quality of life of ART-conceived adults. This study explores the contributions of being conceived with ART and psychosocial cofactors present in young adulthood to the quality of life of adults aged 22–35 years. Young adults conceived through ART or natural conception (NC) completed questionnaires which included a standardized measure of quality of life (World Health Organization Quality of Life – Brief assessment (WHOQoL-BREF)) when aged 18–28 years (T1) and again when aged 22–35 years (T2). The WHOQoL-BREF has four domains: (i) Physical, (ii) Psychological, (iii) Social relationships and (iv) Environment. A total of 193 ART-conceived and 86 NC individuals completed both questionnaires. When accounting for other cofactors in multivariable analyses, being ART-conceived was strongly associated with higher scores (better quality of life) on the Social relationships, and Environment WHOQoL-BREF domains at T2. In addition, less psychological distress, a better relationship with parents, a better financial situation, and perceptions of being about the right weight at T1 were associated with higher scores on one or more of the WHOQoL-BREF domains at T2. In conclusion, being ART-conceived can confer advantages in quality of life in adulthood, independent of psychosocial cofactors.

Maternal-fetal attachment and anxiety in pregnant women who conceived through assisted reproductive technology: A longitudinal study.

BackgroundPregnancy through assisted reproductive technology (ART) is a stressful experience that may affect prenatal attachment. However, maternal-fetal attachment (MFA) and anxiety in pregnancy after ART are understudied in Iran.ObjectiveTo compare changes in MFA and pregnancy-related anxiety (PRA) in the first and third trimester of pregnancy in women who conceived through ART compared to those who conceived naturally.Materials and MethodsThis longitudinal study was conducted in 2019 with 187 pregnant women (ART conception = 43, natural conception = 144). Participants were recruited using the consecutive sampling method from a prenatal clinic in Tehran. The Cranley MFA Scale and the Van Den Bergh PRA Questionnaire were used to collect the data.ResultsThe MFA score in the 12 wk of gestation was lower in the women who conceived with ART compared to in the women who conceived naturally, but there was no statistically significant difference between the groups in wk 36. MFA in both groups was significantly higher at gestational wk 36 than wk 12 (p 0.001). The increase in MFA score was significantly higher in the women who conceived with ART than in those who conceived naturally (p 0.001). The anxiety score declined in the two groups and no statistically significant difference was observed in the changes of anxiety scores between the two groups (p = 0.84).ConclusionPregnant women who conceived through ART were as attached to their fetus in the third trimester of pregnancy as other women and did not experience more PRA.

Early Postpartum Glucose Intolerance, Metabolic Syndrome and Gestational Diabetes Mellitus Determinants after Assisted Conception: A Prospective Cohort Study.

Background:This study aimed to determine the prevalence of postpartum metabolic syndrome (MetS), glucose intolerance, and the determinants, 6-12 weeks postpartum in women with assisted reproduction technology conception gestational diabetes mellitus diagnosis (ART-GDM) compared to women with spontaneous conception and GDM diagnosis (SC-GDM).Materials and Methods:In this prospective cohort study, two groups consisting of 62 ART-GDM and 64 SC-GDM singleton pregnant women were followed 6-12 weeks after delivery for postpartum MetS. Fasting glucose, 75-g 2-h OGTT, and lipid profile were assessed. Waist and hip circumference, and systolic and diastolic blood pressures (BP) were measured at postpartum. Clinical, paraclinical, and obstetric data were recorded from registry offices. The prevalence of MetS and glucose intolerance were determined. Predictors of MetS and glucose intolerance were evaluated by logistic regression.Results:The prevalence of postpartum MetS was 20.8% in ART-GDM women and 10.9% in SC-GDM (P=0.123). Mean postpartum BMI and systolic BP were significantly higher in the ART-GDM group (P=0.016 and P=0.027 respectively). Adverse pregnancy outcomes were significantly higher in the ART-GDM group. Postpartum glucose intolerance prevalence did not vary significantly between the groups. Family history of diabetes was a predictive factor for postpartum MetS and glucose intolerance 6-12 weeks after delivery.Conclusion:Early postpartum MetS and glucose intolerance prevalence after assisted conception did not vary significantly; however, postpartum body mass index (BMI) and systolic BP were significantly higher in the ART-GDM group. Lifestyle modification programs and long-term health care of ART women with GDM diagnosis can be recommended. Further studies with larger sample size and longer follow-up are necessary to verify our findings.

Genome-Wide Analysis of DNA Methylation in Buccal Cells of Children Conceived through IVF and ICSI.

Early life periconceptional exposures during assisted reproductive technology (ART) procedures could alter the DNA methylation profiles of ART children, notably in imprinted genes and repetitive elements. At the genome scale, DNA methylation differences have been reported in ART conceptions at birth, but it is still unclear if those differences remain at childhood. Here, we performed an epigenome-wide DNA methylation association study using Illumina InfiniumEPIC BeadChip to assess the effects of the mode of conception on the methylome of buccal cells from 7- to 8-year-old children (48 children conceived after ART or naturally (control, CTL)) and according to the embryo culture medium in which they were conceived. We identified 127 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) (FDR < 0.05) with low delta beta differences between the two groups (ART vs. CTL). DMPs were preferentially located inside promoter proximal regions and CpG islands and were mostly hypermethylated with ART. We highlighted that the use of distinct embryo culture medium was not associated with DNA methylation differences in childhood. Overall, we bring additional evidence that children conceived via ART display limited genome-wide DNA methylation variation compared with those conceived naturally.

Association Between Assisted Reproductive Technology and White Matter Injury in Premature Infants: A Case-Control Study.

Objectives: Whether there is a link between assisted reproductive technology (ART) and brain damage in premature infants remains unclear. The aim of this study was to determine whether premature infants conceived by ART are at a greater risk of developing white matter injury (WMI), as detected by magnetic resonance imaging (MRI) or diffusion-weighted imaging (DWI) within 14 days, than those naturally conceived (NC).Methods: A retrospective case-control study was conducted on singleton premature infants with a gestational age of ≥28 weeks and <34 weeks delivered between 2017 and 2019 at Shengjing Hospital, China Medical University. This study included 638 live births that were stratified into case group (n = 218) and control group (n = 420), depending on the presence or absence of WMI. The exposure proportion of ART was compared between the case and control groups, and a logistic regression model was used to identify whether ART was an independent risk factor for WMI.Results: In the univariate analysis, the exposure proportion of ART conception was higher in cases than in controls (12.84 vs. 7.38%, p = 0.024). According to the multivariable analysis, after adjustment for other variables, the association between ART and WMI remained significant (1.82; 95% confidence interval, 1.04–3.21; P = 0.038).Conclusions: Singleton premature infants conceived by ART have a higher risk of WMI than NC infants. Given that ART is an independent risk factor for WMI in premature infants, more attention should be paid to neurodevelopmental outcomes in this group.